This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The use of siRNA for the treatment of various diseases, including cancer and ocular ailments, is a remarkably promising area of research, although new and more efficient delivery methods are still needed. Proposed herein is the development of a new class of chiral polyamines for siRNA complexation and delivery. These polyamines contain several features that are expected to lead to high binding affinities with siRNA, including cationic amines, hydrophobic side chains, and well-defined three-dimensional configurations dictated by the chiral side chains. Moreover, the polyamines contain fluorescent substituents that will allow for the direct imaging of the siRNA-polyamine complexes in cellular environments. The complexation of the polyamines with a model siRNA will be measured using a variety of analytical techniques, and the success of the polyamines in complexing and delivering siRNA will be measured using an in vivo assay with mouse NIH 3T3 cells. The successful transfection of siRNA using these notoriously difficult to transfect cells will demonstrate the advantages of these new polyamines for siRNA complexation and delivery. The siRNA that will be transfected is one targeted against hnRNPA1 expression, which is an RNA-protein complex involved in PKM gene regulation. Aberrant expression of hnRNPA1 has been implicated in a variety of cancers. As such, targeting hnRNPA1 using siRNA will enable the development of new and effective disease treatments.